Monoclonal antibody therapy
A clinical reference covering monoclonal antibody (mAb) mechanisms, INN nomenclature, unique pharmacokinetics (TMDD, FcRn recycling), immunogenicity and anti-drug antibodies, infusion reaction management, and biosimilar considerations.
Major monoclonal antibody classes in clinical use
| Target | Example drugs | Mechanism | Key indications |
|---|---|---|---|
| TNF-α | Adalimumab, infliximab, etanercept* | Neutralise soluble TNF-α | RA, IBD, psoriasis, AS |
| IL-6/IL-6R | Tocilizumab, sarilumab | Block IL-6 receptor signalling | RA, CRS, giant cell arteritis |
| IL-4Rα (IL-4/IL-13) | Dupilumab | Block IL-4 and IL-13 signalling | Atopic dermatitis, asthma, CRSwNP, PN |
| PD-1 / PD-L1 | Pembrolizumab, nivolumab, atezolizumab | Restore T-cell anti-tumour immunity | NSCLC, melanoma, TNBC, and many others |
| HER2 (ERBB2) | Trastuzumab, pertuzumab | Receptor blockade + ADCC | HER2+ breast cancer, gastric cancer |
| CD20 | Rituximab, obinutuzumab, ofatumumab | B-cell depletion (ADCC + CDC) | NHL, CLL, RA, MS |
| VEGF / VEGFR | Bevacizumab, ramucirumab | Inhibit tumour angiogenesis | CRC, NSCLC, glioblastoma |
| IgE | Omalizumab | Neutralise free IgE | Severe asthma, urticaria, food allergy |
| CGRP/CGRPR | Erenumab, fremanezumab, galcanezumab | Block CGRP pathway | Migraine prevention |
| PCSK9 | Evolocumab, alirocumab | Prevent LDL receptor degradation | Hypercholesterolaemia |
* Etanercept is a fusion protein (not strictly an antibody) but often grouped with TNF inhibitors
mAb pharmacokinetics: what makes biologics different
Monoclonal antibody PK differs fundamentally from small-molecule drugs — due to size, route of administration, FcRn recycling, and target-mediated elimination.
Route and SC bioavailability
mAbs are not orally bioavailable (proteolysis in GI tract, MW ~150 kDa). SC injection bioavailability is typically 50–80%, with absorption via the lymphatic system. IV infusion achieves 100% bioavailability but requires healthcare setting access. Subcutaneous autoinjectors have increased patient self-administration (adalimumab, evolocumab, dupilumab). See oral bioavailability glossary.
FcRn recycling and long half-life
The neonatal Fc receptor (FcRn) rescues IgG from lysosomal degradation by binding at low pH in endosomes and releasing at neutral pH in the bloodstream. This recycling mechanism gives IgG1 mAbs a half-life of ~21 days — far longer than small molecules. Engineered Fc variants (YTE mutations, LS mutations) further extend half-life to 6–12 weeks (nirsevimab, tezepelumab). See half-life glossary.
Target-mediated drug disposition
When a mAb binds its membrane-bound target, receptor-mediated endocytosis can eliminate the drug-target complex. At low drug concentrations, TMDD dominates — producing non-linear, dose-dependent PK. At higher concentrations (target saturation), TMDD saturates and PK becomes linear. This is why mAb dose-concentration relationships can be non-proportional at low doses. See non-linear pharmacokinetics.
Volume of distribution and tissue penetration
mAbs have small Vd (~3–8 L for IgG1 — approximately plasma + interstitial fluid volume). They do not penetrate intracellularly or cross the blood-brain barrier under normal conditions. CNS-targeting mAbs (lecanemab, donanemab for Alzheimer's) require IV administration and achieve modest CNS concentrations. Subcutaneous dosing sites can affect local tissue drug concentrations. See volume of distribution glossary.
Administration routes and dosing frequencies of selected mAbs
| Drug | Route | t½ | Typical interval | Setting |
|---|---|---|---|---|
| Adalimumab | SC | ~14 days | Q2W | Self-injection / homecare |
| Infliximab | IV infusion | ~8–10 days | Q8W (maint.) | Infusion centre |
| Pembrolizumab | IV infusion | ~27 days | Q3W or Q6W | Oncology infusion unit |
| Dupilumab | SC | ~21 days | Q2W | Self-injection |
| Trastuzumab | IV or SC | ~28 days (IV) | Q3W | Oncology / homecare (SC) |
| Evolocumab | SC | ~11–17 days | Q2W or Q4W | Self-injection |
| Nirsevimab | IM (single dose) | ~71 days (LS Fc) | Once per RSV season | Paediatric clinic |